Not all of my patient interactions are easy. One of my colleagues, after reading my blog, remarked, “It sounds like you have really easy patients.” While that’s true for the most part, of course there are more difficult patients, as in any practice. Some patients, eager to get into treatment to stop opioid addiction, may not be at all ready to stop other drugs of addiction. That’s not a deal-breaker for me, unless those drugs could be fatal when mixed with methadone or buprenorphine. This means the use of alcohol, benzodiazepines, and sedatives of other kinds must be discussed in detail.

I’ve noticed a conversational merry-go-round that I call “the benzo conversation.” I’ve had versions of this conversation more times than I can remember.

This conversation occurs during my initial assessment of a new patient presenting for medication-assisted treatment. I always look on my state’s prescription monitoring program for each new patient on the day of admission. If they have prescriptions for benzodiazepines (like Xanax, Valium, or clonazepam), or other sedatives (Soma, Ambien, etc.) I need information about the pattern of use. Is my patient taking his prescribed daily dose? Is he then physically dependent on benzodiazepines? Is he selling them? Is he giving part of the prescription away, and taking the rest? Does he binge on benzos for the first few weeks of the month, and then run out for several weeks? Or is he bartering the benzos for opioids, and not taking any of them, despite filling a large prescription each month?

I really don’t care if the patient is breaking the law or not; I just want to get the complete picture of my patient’s health status.

Following is a typical conversation with a new patient whom I will call “Bob.”

Bob sought admission to our methadone maintenance treatment program for his opioid addiction. He had snorted pain pills for six years, and wanted help. He had little if any denial about his opioid addiction. He denied taking any prescription medications, saying he got all his opioids off the street, used no other drugs or medications, and had no other medical problems.

However, when I checked his name on my state’s controlled prescription monitoring program, he was filling a prescription for Xanax 2mg, ninety per month, from a local Dr. Feelgood. This prescription had been filled every month for the last four years. My patient’s admission urine drug screen also tested positive for benzodiazepines.

As part of my initial history and physical, I asked him about the Xanax prescription. I explained to Bob that benzos have the potential to cause a fatal overdose when mixed with opioids. I told him that benzos are especially risky with methadone, and I was concerned about his use of them.

Bob said, “Oh, I don’t use benzos now. I haven’t used Xanax for years.
“But you’ve been prescribed it every month and picked up the last prescription of ninety pills just two weeks ago.”
“Yes, but I don’t take them. I quit them long ago.”
“And you do have benzos in the urine sample you gave us.”
“Well, that’s probably from a little piece of Valium I used four days ago.”
“Ummm…, Valium’s also a benzo, in the same family as Xanax, so when you say you’ve stopped, that doesn’t make sense to me.…”
“As I told you, I don’t take benzos anymore.”
“But four days ago is pretty recent.”
“No,” he said, getting a little worked up. “As I’ve already told you, I stopped benzos years ago!”
“So what do you do with the Xanax pills you pick up at the pharmacy every month?”
“I don’t know. They’re in the house somewhere. But I don’t take them.”
“So you have…how many bottles do you have at home?”
“Bunches, I don’t know.”
I could tell I was annoying him, but this as an important clinical issue, so I pushed on.
“Would you be willing to bring all those bottles in tomorrow so the nurse can watch you dispose of them?”
He sighed deeply, annoyed by my questions. “Yes. I suppose I can. Now can I get my dose?”
“No, I’ll leave an order for you to be able to start tomorrow after you bring in the medication to dispose, since you tell me you haven’t taken them. I worry about a fatal overdose if methadone were combined with all that Xanax you have at home.”
Now he was mad. “I don’t have any Xanax at home! I’m not going to overdose! I know what I’m doing.”
“Will you give me permission to call the doctor prescribing the Xanax, so we can talk about your entry into treatment here? Maybe your doctor would be willing to taper your dose so that we can make it safer for you to be in treatment with us.”
“No! I don’t want everybody to know my business. My doctor is friends with my ex-wife and if she finds out I’m being treated for addiction, she’ll cause trouble. He can’t find out.”
“I’m sorry, but that’s a deal-breaker for me. I’m not going to prescribe methadone for you unless I can talk to your other doctor. It’s just too risky. All of your doctors need to know all medications that you’re on.”
“So you’re telling me to go back out there and use drugs? That I can’t get help unless my ex-wife finds out I’m an addict?” The veins in his neck were standing out.
“No. I’m not telling you to use drugs. I’m telling you…
“I want my money back, since I’m gonna have to go buy dope again ‘cause you won’t help me. It’s just not right. I came here to get help.” He stalked off toward the receptionist, where I heard him demanding his money back, despite the hour he spent with a counselor and the time spent with me in an evaluation. (For some reason, patients who don’t get admitted to the program don’t feel they should have to pay for their evaluation)

This was a difficult, tense conversation, and one I’ve had too many times to count. This patient wasn’t a bad guy, but he was not ready to address his benzodiazepine use. The outcome wasn’t what I’d hoped, and this patient didn’t come into treatment.

There’s no way I could know what this patient was doing with his benzodiazepine prescription. I couldn’t tell if this patient was telling the truth, in denial, or lying. Without being able to talk to his prescribing doctor, I wasn’t willing to start medication-assisted treatment. This didn’t mean he didn’t need treatment, only that perhaps a different form of treatment will be safer for him. I wish I could have given him information about other treatments, but he left too quickly and too angrily.

Sometimes patients tell me I’m violating their privacy by looking at their information on the prescription monitoring database. I tell them I don’t see it that was at all, since they are asking me to prescribe a medication that could have a fatal interaction with other medications. Not only is it my business, it’s my responsibility.

Some doctors would fault me for not admitting this patient despite his refusal to allow me to talk to his prescribing doctor, given the increased risk of death for patients in active opioid addiction who are not in any treatment. But I would feel terrible if I’d admitted this patient and he died during the first few weeks of a methadone/benzodiazepine overdose. Either way, there’s a lot at stake, and I feel stress about these decisions.

You say you don’t know the Sackler family? I’ll remind you. They own one-hundred percent of Purdue Pharma, a pharmaceutical company best known for manufacturing their block-buster drug OxyContin.

This is a bitter pill for me to swallow.

I started working in the field of opioid addiction treatment in 2001. At that time, nearly every opioid addict I saw was using OxyContin as their main drug. Opioid addiction in general and OxyContin addition in particular plagued many small towns and rural areas where I worked.

OxyContin was widely prescribed for pain. This powerful drug was advertised as “The one to start with and the one to stay with,” during sales pitches to rural physicians. OxyContin flooded the black market. Opioid addict quickly discovered OxyContin’s time-release coating could be easily defeated, and the pill was often snorted or injected for the rush of opioid euphoria it produced.

I was certainly not the only doctor to notice the rise of OxyContin addiction.

Barry Meier’s book Pain Killer: A “Wonder” Drug’s Trail of Addiction and Death (Rodale Books, 2003), tells the story of small town doctors trying to get the attention of Purdue Pharma, the government, or anybody else who could help change the destruction OxyContin was doing to Appalachia around that time.

I remember attending a pain and addiction conference around sometime around 2003 or 2004. At the end of the lecture explaining how opioids could be prescribe safely, a doctor from Virginia dared to ask the experts something along the lines of, “What are we going to do about OxyContin?” I thought to myself that I was glad someone had finally said what I was thinking.
This was a long time ago; I don’t remember exact words, but my memory is that he was soundly rebuffed for daring to mention one specific drug by name. He was scolded and told that the real problem was with opioids in general, and one drug company (who happened to have some of the lecturers on their payroll) should not be singled out as the problem.

I remembered wishing those experts could spend a day at my treatment program talking to the OxyContin addicts.

Eventually, the U.S. General Accounting Office asked for a report about the promotion of OxyContin by Purdue Pharma. By 2002, prescriptions written for non-cancer pain accounted for 85% of the OxyContin sold, despite a lack of data regarding the safety of this practice. By 2003, primary care doctors, with little or no training in the treatment of chronic non-cancer pain, prescribed about half of all OxyContin prescriptions written in this country. By 2003, the FDA cited Purdue Pharma twice for using misleading information in its promotional advertisements to doctors. [1, 2] Purdue Pharma also trained its sales representatives to make deceptive statements during OxyContin’s marketing to doctors. [3]

Testifying before Congress in 2002, a Purdue Pharma representative said the company was working of re-formulating OxyContin, to make it harder to use intravenously. This representative claimed it would take several years to achieve this re-formulation. The re-formulated OxyContin was finally approved by the FDA in 2010, eight years later. Currently, this medication forms a viscous hydrogel if someone attempts to inject or snort the medication. It isn’t abuse-proof; probably no opioid will ever be so, but it is much more abuse-deterrent than the original.

Did Purdue Pharma drag their feet in this re-formulation? Experts like Paul Caplan, executive director for risk management for the drug company, said there were issues about the safety of incorporating naloxone into the pill to make it less desirable to intravenous addicts. He also pointed out that some delay in approval was due to the FDA.

For comparison, Sterling Pharmaceutical, when it became widely known patients were abusing their pain medication Talwin, re-formulated within a year, adding naloxone to the medication and reducing its desirability on the black market. Since this was in the 1980’s, I would assume there was less technology to help back then, compared to 2002.

I’ll let readers draw their own conclusions.

In May of 2007, three officers of Purdue Pharma pled guilty to misleading the public about the drug’s safety. Their chief executive officer, general counsel, and chief scientific officer pled guilty as individuals to misbranding a pharmaceutical. They did no jail time but paid $34.5 million to the state of Virginia, where the lawsuit was brought.

The Purdue Pharma Company agreed to pay a fine of $600 million. Though this is one of the largest amounts paid by a drug company for illegal marketing, Purdue made 2.8 billion dollars in sales from the time of its release in 1996 until 2001.

None of the Sackler family members were charged, because they were not involved in the day to day running of the company.

These parents are lobbying to make this drug illegal in Georgia, where its use is presently not against the law.

Kratom (also called ketum or kratum) is a tree in the genus Mitrogyna, which is related to the coffee tree, and found in Southeast Asia. Kratom leaves have been used for thousands of years by natives of the area to produce stimulant and opioid effects. Fresh leaves can be chewed, or broken up to make a drink, or steeped in hot water to make a tea. Dried leaves can be smoked by users, who say low doses of kratom cause a stimulant effect. Higher doses are said to cause sedation.

Kratom’s active ingredient is mitragynine, an opioid agonist. Mitragynine activates the mu opioid receptor in the human brain to cause an opioid-like effect. Like other opioids, this compound in the kratom tree relieves pain and causes euphoria. Some rat studies demonstrated more potent analgesia from mitragynine than morphine. It’s structurally different than other opioids, and unlikely to show as an opioid on drug testing.
Because of its opioid-like effects, kratom can be used recreationally for the high it produces.

If you google “buy kratom,” more than a million websites appear, offering to sell all sorts of varieties of kratom, and extolling its properties of, “Pain relief, Energy, Prolonged Sexual Intimacy, and Mood Support.” You can buy capsules, dried leaves, and plant extracts. Because of this recreational use, governmental agencies in the U.S. have been reluctant to fund studies on this drug.

Sadly, many people accept the idea that “herbal” and “natural” means “safe.” Not so at all. Some of the world’s most potent poisons are found in nature. Hemlock, belladonna, and cyanide leap to mind. And there’s no way to know what exactly you are buying on the internet. It may be kratom, ….or it may be nightshade.

Assuming a person does buy real kratom off the internet – is it harmful? Probably about as harmful as other opioids, though rat studies did show less respiratory depression than other opioids. That may be due to kratom’s activity at the kappa opioid receptor. This drug also has adrenergic and serotonergic activity, so it has a complicated method of action. The increased adrenergic effect of the drug may give users a feeling of energy, like the other stimulants cocaine and amphetamines. This property has led some people to say kratom could be a treatment for methamphetamine addiction.
Chronic and continued use of the kratom leaf can cause opioid dependence, with opioid-type physical withdrawal symptoms when stopped. However, at least one case report showed less physical withdrawal than expected when a heavy user suddenly stopped kratom after having a seizure. [1] There’s talk on internets sites of using kratom as a treatment for opioid addiction, but no scientific literature or human trials have been done.

Mitragynine from the kratom tree has intriguing possibilities for use in the medical world, but we won’t know unless scientific studies are done. Until then, it would be dangerous and irresponsible to recommend use of this product, especially if it’s bought off the internet with no way to know what you are buying.

I hope researchers will explore this drug to see if it has potential to help patients with opioid addiction. For now, there’s not enough evidence to be able to recommend kratom’s use for any purpose. And with recent publicized adverse events, there’s good reason to avoid kratom, given it’s potential to cause physical dependence and addiction.

Even if the compound mitragynine in kratom shows efficacy in clinical trials as a pain reliever or opioid addiction treatment, it shouldn’t be ingested in unprocessed plant form. We don’t have people in pain chew on an opium poppy seed pod, or heart patients chew on the foxglove plant to get their digitalis, and doctors won’t recommend use of kratom in the plant form. Let’s purify the drug in kratom, mitragynine, study it, and produce it as a medication in standardized doses with quality control, if it’s found to be effective.

Tramadol, the generic for the brand name Ultram, is a messy drug. It’s a pain reliever that has actions on several types of brain receptors: the mu opioid, serotonin, norepinephrine, NMDA, and other receptors.

Because it stimulates the mu opioid receptors, it can cause feelings of pleasure as well as pain relief. Tramadol is far less active at the mu opioid receptors than its metabolite, and it takes time for the tramadol to be metabolized in the liver to its first metabolite. Because of this delay, some experts thought it wouldn’t appeal to addicts, who prefer an immediate high. Overall this is probably true, and tramadol has a much lower rate of addiction than other opioids, but it still causes addiction in some patients.

Some of tramadol’s pain relieving properties may also be produced by its actions on serotonin and norepinephrine receptors, since tramadol’s pain relieving capability is only partially reversed by a pure opioid antagonist like naloxone.

When this medication was first released, it wasn’t a controlled substance. That is, the DEA didn’t control it strictly like medications that can cause addiction. Now, it’s a Schedule IV drug, in some states. It does have some benefit for pain relief, but also some risk of addiction, though lower than that of hydrocodone, for example.

Tramadol is usually dosed in 50mg pills, one or two every six hours, giving the maximum dose of 400mg per day. Recreational use of this medication (to get high) is dangerous, since it causes seizures at doses higher than 400mg. In susceptible patients, it can even cause seizures at lower prescribed doses.

I’ve seen patients in tramadol withdrawal who were so sick it frightened me. This drug can produce a severe withdrawal. If a patient taking high doses stops taking tramadol suddenly, some patients have opioid withdrawal symptoms like sweating, nausea, diarrhea, high blood pressure and heart rate, and severe muscle and joint pains. The sickest patient I’ve ever seen in opioid withdrawal had been using only tramadol, in doses of around 600mg per day. She had fever to 103 degrees, and dehydration from the diarrhea and vomiting. That patient needed hospitalization.

Besides the opioid-withdrawal symptoms, some of these patients also have withdrawal symptoms similar to those seen when certain serotonin-affecting antidepressants, like Paxil and Celexa, are stopped suddenly. They can have fairly severe anxiety, depression, mood swings, and restlessness. Many times they have weird sensory experiences, often called “brain zaps,” or the sensation of electric shocks throughout the body. They can have seizures during this withdrawal.

If the patient had only physical dependency and no addiction, the dose of tramadol can usually be tapered slowly over a few weeks to months, as an outpatient. But if the patient has not only physical dependency but also the disease of addiction, the obsession and craving for the medication will usually prevent a successful outpatient taper, unless a dependable non-addict holds the pill bottle, and dispenses it as prescribed.

Traditional treatment for tramadol addiction starts with detoxification. As above, that can rarely be done as an outpatient, so medical inpatient detoxification admissions for five to seven days can be helpful. However, since tramadol acts so much like an opioid, patients ready to leave detox probably need to go on to an inpatient residential treatment center for at least thirty days. Intensive outpatient treatment probably isn’t enough support for these addicts. But that’s only my opinion, since I haven’t found any studies describing success rates with tramadol addicts.

Opioid maintenance medications like methadone and buprenorphine do stop the opioid-type withdrawal symptoms from tramadol, but there’s no information about the use of maintenance medications in these patients. Most doctors working in clinics won’t start a patient on maintenance medications unless the patient is also using other opioids.

Often, methadone patients at the opioid treatment centers where I work are given tramadol by their primary care doctors who think it’s a low risk medication for opioid addicts. It probably is lower in its risk for abuse, but it can cause withdrawal in patients on stable, blocking doses of methadone. [1]

Tramadol is a synthetic, pared-down version of codeine. Interestingly, a structurally similar medication, tapentadol, has just been released, and is now being sold under the brand name Nucynta. That medication is a schedule II drug, presumably because of a higher abuse potential than we’ve seen with tramadol. Tapentadol stimulates opioid mu receptors, and also acts as a norepinephrine re-uptake inhibitor, like some antidepressants.

I saw my first patient who was addicted to Nucynta earlier this year. He had a history of opioid addiction in the past, had successfully tapered off methadone maintenance, but became re-addicted to opioids during a bout of back pain. He couldn’t stop taking Nucynta without abusing other illicit opioids to ease his withdrawal symptoms. Because he was using other opioids, I did admit him to methadone maintenance and he continues to do well on our program.

The bottom line is this: if you are in recovery from addiction (alcohol or drugs, this medication should be used with caution. Let your doctor know that you’re in recovery from addiction. If you must take a potentially addicting medication, talk to your sponsor and your support network. Go to extra meetings. Let a dependable non-addict hold the pill bottle and dispense as prescribed. If you have to take the medication for more than a few weeks, have your doctor taper your dose instead of stopping suddenly.

Recent news reports have denounced rates of opioid prescribing for war veterans. According to the Center for Investigative Reporting, rates of opioid prescribing by VA doctors have increased two hundred and seventy percent over the last twelve years. The VA is now prescribing more than one opioid prescription for each patient it treats. (1)

The dramatically different opioid prescribing rates between different VA systems are concerning. For example, doctors at a VA hospital in Oklahoma prescribed 160.7 opioid prescriptions for every one hundred patients, compared to doctors at a VA hospital in Manhattan, who prescribed 19.8 opioid prescriptions for every one hundred VA patients treated. That’s more than an eight-fold difference.

Of particular interest, out of the 130 VA systems evaluated, Mountain Home, Tennessee, ranked as the sixth most frequent prescriber of opioids. Located in Johnson City, TN, this VA system had a rate of 138.8 opioid prescriptions per 100 patients for 2012. The worst system was Muskogee, OK, with 160.7 per 100 patients, followed closely by Beckley WV, Lexington, KY, and Huntington, WV. (But remember, Tennessee’s Department of Mental Health said there was no need for an opioid treatment center to be located in Johnson City. Nope. No problem there.)

We already know that in some states, the numbers of U.S. citizens who die from drug overdoses outnumber deaths from motor vehicle accidents. But veterans treated by VA doctors die from prescription drug overdoses at almost twice the rate of civilians. (1)

To be fair, we need to consider the changing nature of war injuries. Soldiers are surviving catastrophic injuries which would have been fatal in the past. This is partly due to better body armor and partly because of better and quicker medical care at the time of the injury. Some experts say some Iraq and Afghanistan soldiers have survived severe burns and amputations that killed Vietnam-era soldiers.

These patients surely need heavy opioids, at least early in their treatment. No compassionate doctor would skimp on pain medication for an acutely injured person. But acute pain is different from chronic pain. As the patient recovers, it’s time to consider backing off on opioids, and consider trials of non-opioid means of pain control. Patients often need help getting off prescribed opioids, which may mean tapering them over weeks to months, in order to prevent opioid withdrawal. This often takes more time and patience than writing another opioid prescription.

Due to the nature of the Iraq and Afghanistan wars, thousands of veterans have been diagnosed with traumatic brain injury (TBI). We are only beginning to understand the relationship between TBI and the risk for developing addiction. Similarly, war veterans have higher rates of PTSD (post-traumatic stress disorder) and depression. These mental disorders increase the risk for developing addiction to drugs including alcohol in all people, including war veterans.

I’ve admitted a few war veterans to the opioid treatment programs where I work. I dread trying to coordinate care with their VA doctors. Many times, after getting a release from the patient, I’ve called the VA to talk with their doctor. I can’t think of one time when I’ve reached the doctor to whom I wanted to speak. Sometimes I got a nurse, and left a message for the doctor to call me back, knowing I’d never hear from them.

I don’t have any way to know what those VA doctors are prescribing for my patients. Often, at least in my area, it’s a heavy benzodiazepine or two, and one or more opioids. Because the VA doesn’t report medication to my state’s prescription monitoring program, I’m left in the dark. I hear that’s supposed to change, but not soon enough for me.

The VA can fix this problem of inappropriate prescribing. I’ve been at ASAM (American Society of Addiction Medicine) conferences, and have met knowledgeable VA physicians. I’ve heard them lecture at these meetings. The VA must allow these experts teach their colleagues who are dated or oblivious in their prescribing habits.

I hope to see the time come when it’s as easy for a war veteran to access treatment for addiction as it is to get opioid prescriptions. These treatments should, of course, include medication-assisted treatments with buprenorphine and methadone.

Suboxone is getting competition from the generic preparations of buprenorphine/naloxone, and now another name-brand preparation has just been approved by the FDA.

It’s called Zubsolv, and the manufacturer, Orexo, says it takes less time to dissolve, is a smaller tablet, and tastes better. The company added a menthol taste. They also say their preparation has higher bioavailability, and the tablets come in two strengths: 5.7/1.4 buprenorphine to naloxone ratio, and 1.4/.36 ratio. The lower doses of buprenorphine per tablet are due to the higher bioavailability. Also, each tablet is contained in unit dose packaging, to reduce the risk of pediatric exposures.

Interestingly, the package insert says not to switch from one buprenorphine preparation to another, because other tablets have different amounts of buprenorphine than Zubsolv. That’s a problem for established patients. I’d like the manufacturer to give prescribers some information on how blood levels of their tablets compare to blood levels of other preparations of buprenorphine. I guess new patients could be started on Zubsolv.

On the company’s website, they claim that nine out of ten people prefer Zubsolv to Suboxone.

This medication should be available in pharmacies by September of this year.

I’m glad for every new buprenorphine product that’s released to the market, because I hope it brings the price down. Lower cost of medication means more opioid addicts could afford treatment.

I’m curious to see how this new preparation will be greeted by patients on buprenorphine.

I’ve blogged about states that have passed new laws addressing the prescribing of opioids, but the manufacturers of prescription opioids medications also have made changes to help reduce the potential for medication misuse. Of course, opioids will never be misuse-proof, but at least it’s a little harder to misuse some of the newer ones.

Oxecta is a new immediate-release brand of the drug oxycodone. It’s formulated so that it breaks into chunks when crushed, instead of a powder. When it’s mixed with water, it forms a gel so that it can’t be injected. This pill contains sodium laurel sulfate, a substance that irritates the nose if snorted.

Lazanda is a new delivery form of a very potent opioid, fentanyl. This brand is designed to be used as a nasal spray, which I would expect to be very addictive. The preparation itself has no anti-abuse features, but in order to distribute, dispense, prescribe, or be prescribed this medication, parties have to sign an agreement and be enrolled with the drug company. This extra scrutiny is hoped to deter diversion by distributor, pharmacy, doctor, or patient. Physicians must take a training program specific for this brand, and be enrolled with the drug company as a prescriber, or pharmacies can’t dispense to the patient.

Patients also need to complete a patient-prescriber agreement. Many people (like me) think doctors aren’t likely to jump through these extra hoops to prescribe this particular brand, when other brands of the same medication are already on the market, though not in the form of nasal spray.

Remoxy, another brand of oxycodone, hasn’t yet been FDA approved. Supposedly, it’s resistant to injection or snorting, and also has been formulated to be resistant to alcohol extraction.

Drug companies are now required by the FDA to have plans to evaluate and mitigate the risks associated with the opioid drugs they manufacture, particularly if they make sustained release or long-acting opioid preparations. This cooperation by drug manufacturers is a necessary part of turning the tide of opioid addiction in this country.

Last year, Purdue Pharma re-formulated OxyContin, making it more difficult to crush to snort or inject. I noticed a sudden drop-off in patients entering treatment for pain pill addiction who said OxyContin was their drug of choice. During the years 2002 through 2007, nearly all of the opioid addicts I admitted to treatment said OxyContin was their preferred drug. It became obvious that the re-formulation made a big difference.

Addicts can and will still abuse these medications orally to get high, but the new formulations really do reduce abuse by making pills less likely to be snorted or injected.